rs317807

chr18-57583438-G-Achr18-57583438-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000140.5(FECH):c.67+3116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,174 control chromosomes in the GnomAD database, including 6,142 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6142 hom., cov: 33)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538

Genes affected

FECH (HGNC:3647): (ferrochelatase) The protein encoded by this gene is localized to the mitochondrion, where it catalyzes the insertion of the ferrous form of iron into protoporphyrin IX in the heme synthesis pathway. Mutations in this gene are associated with erythropoietic protoporphyria. Two transcript variants encoding different isoforms have been found for this gene. A pseudogene of this gene is found on chromosome 3.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FECH	NM_000140.5	c.67+3116C>T		intron_variant		ENST00000262093.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FECH	ENST00000262093.11	c.67+3116C>T		intron_variant		1	NM_000140.5

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40008 AN: 152056 Hom.: 6142 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.291

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 40013 AN: 152174 Hom.: 6142 Cov.: 33 AF XY: 0.267 AC XY: 19848 AN XY: 74388

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.294

Alfa AF: 0.266 Hom.: 1003

Bravo AF: 0.259

Asia WGS AF: 0.486 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.4
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs317807; hg19: chr18-55250670;